NAFLD, NASH - Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver
Conditions
Brief summary
Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is an increasingly recognized complication of obesity, with prevalence estimates of about 30% of individuals in the United States. A subset of these will develop progressive disease in the form of nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver failure. The investigators hypothesize that LUM-201 (Ibutamoren mesylate) will decrease intrahepatic lipid accumulation as quantified by proton magnetic resonance spectroscopy (1H-MRS).
Interventions
DRUGLUM-201
LUM-201 (ibutamoren mesylate) is an oral growth hormone secretagogue.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label study with historical controls.
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 21-60yo and generally healthy 2. BMI ≥ 25 kg/m2 3. Radiographic or histologic diagnosis of NAFLD / NASH 4. Insulin-like growth factor-1 (IGF-1) level \<3rd quartile of normal for age
Exclusion criteria
1. Contraindications to MRI imaging 2. Diabetes mellitus or use of diabetes medications 3. History of cancer, significant renal disease, decompensated or unstable cardiovascular disease 4. Cirrhosis or known liver disease other than NAFLD 5. Pregnancy or breastfeeding 6. Known pituitary or hypothalamic disease affecting the growth hormone axis 7. Chronic use of drugs causing hepatic steatosis in the past 12 months (chronic oral steroids, methotrexate, tamoxifen) 8. Treatment with medications that may interact with LUM-201 (ibutamoren mesylate)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic Lipid Content (IHL, Percent Liver Fat) | 6 Months | Change in intrahepatic lipid content (6-month percent liver fat minus baseline percent liver fat) as measured by proton magnetic resonance spectroscopy (1H-MRS). Outcome is presented as change in percent liver fat. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Inflammation and Fibrosis by LiverMultiScan Corrected T1 (cT1) Score | 6 Months | Change in hepatic inflammation and fibrosis by LiverMultiScan cT1 (6-month cT1 score minus baseline cT1 score). Outcome is presented as change in cT1 score (ms). Higher values indicate more severe combined inflammation and fibrosis (normal range 633-794 ms). |
| Alanine Aminotransferase (ALT) | 6 Months | Change in ALT (6-month ALT minus baseline ALT). Outcome is presented as change in ALT (U/L). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Treatment Open-label study of oral LUM-201 (ibutamoren mesylate) 25mg daily in otherwise healthy adults with BMI ≥25 kg/m2 and histologic or radiologic diagnosis of NAFLD.
LUM-201: LUM-201 (ibutamoren mesylate) is an oral growth hormone secretagogue. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Open-label Treatment |
|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 13 |
| Baseline Liver Fat (Percent liver fat by 1H-MRS) | 18.5 percent liver fat STANDARD_DEVIATION 10.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Intrahepatic Lipid Content (IHL, Percent Liver Fat)
Change in intrahepatic lipid content (6-month percent liver fat minus baseline percent liver fat) as measured by proton magnetic resonance spectroscopy (1H-MRS). Outcome is presented as change in percent liver fat.
Time frame: 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Treatment With Ibutamoren | Intrahepatic Lipid Content (IHL, Percent Liver Fat) | 3.9 absolute change in percentage liver fat | Standard Deviation 6.7 |
Comparison: Subjects treated with open-label ibutamoren (n=7) were compared to historical placebo control subjects studied under identical inclusion criteria and procedures (n=10). The hypothesis is that open-label ibutamoren treatment would lead to a significant decrease in intrahepatic lipid content (IHL) as assessed by proton magnetic resonance spectroscopy (1H-MRS, absolute %IHL).p-value: 0.4t-test, 2 sided
Secondary
Alanine Aminotransferase (ALT)
Change in ALT (6-month ALT minus baseline ALT). Outcome is presented as change in ALT (U/L).
Time frame: 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Treatment With Ibutamoren | Alanine Aminotransferase (ALT) | 8 U/L | Standard Deviation 18 |
Comparison: Subjects treated with open-label ibutamoren (n=7) were compared to historical placebo control subjects studied under identical inclusion criteria and procedures (n=10). The hypothesis is that open-label ibutamoren treatment would lead to a significant decrease in alanine aminotransferase (ALT). There was no power calculation for this small pilot study.p-value: 0.6t-test, 2 sided
Secondary
Hepatic Inflammation and Fibrosis by LiverMultiScan Corrected T1 (cT1) Score
Change in hepatic inflammation and fibrosis by LiverMultiScan cT1 (6-month cT1 score minus baseline cT1 score). Outcome is presented as change in cT1 score (ms). Higher values indicate more severe combined inflammation and fibrosis (normal range 633-794 ms).
Time frame: 6 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-label Treatment With Ibutamoren | Hepatic Inflammation and Fibrosis by LiverMultiScan Corrected T1 (cT1) Score | 39 ms | Standard Deviation 44 |
Comparison: Subjects treated with open-label ibutamoren (n=7) were compared to historical placebo control subjects studied under identical inclusion criteria and procedures (n=10). The hypothesis is that open-label ibutamoren treatment would lead to a significant decrease in hepatic inflammation and fibrosis as assessed by LiverMultiScan corrected T1 (cT1) score. There was no power calculation for this small pilot study.p-value: 0.9t-test, 2 sided